Writing this once so I can stop repeating it across threads. It is about retatrutide, and it is deliberately narrow — everything I am not confident about is marked as such.
The phase 2 numbers were about 24% mean weight loss at 48 weeks on the top dose, with the curve still descending at the end of the study. A curve that has not flattened is a real finding, but it also means the true plateau is unknown, and phase 2 populations are small and selected.
Phase 2 tolerability figures rarely survive contact with phase 3 scale. Triple agonism means three receptor systems generating adverse events, and the dropout column is the one I would read first when the larger trials report.
For anyone tracking the class: GLP-1 alone gets you appetite, GLP-1 plus GIP adds tolerability and lipid handling, and adding glucagon adds expenditure and liver-fat reduction. Each addition also adds a receptor system that can generate side effects.
The narrow version of the question is what the phase 2 dropout pattern implies about how the phase 3 tolerability will read. Numbers rather than impressions, if you have them.
wanda_boise said:The phase 2 numbers were about 24% mean weight loss at 48 weeks on the top dose, with the curve still descending at the end of the study.
That holds where the measurement is reliable. Where it is noisy — and a lot of what gets tracked here is noisy — the same reasoning produces confident nonsense.
wanda_boise said:The phase 2 numbers were about 24% mean weight loss at 48 weeks on the top dose, with the curve still descending at the end of the study.
I would rather people stopped quoting the 24% as if it were a licensed outcome. It is a phase 2 result in a few hundred participants with no cardiovascular endpoint and no long-term safety data, and this board has a habit of treating pipeline numbers as settled.
Trusted third-party HPLC & mass spectrometry analysis. Verify peptide purity with the lab the community relies on. Independent. Accurate. Transparent.
Verify Your PeptidesEst. 1998. The synthesis house behind the vials you send for testing. ISO 9001 and cGMP certified, 1,500+ staff, batch-specific COA with every order.
Browse GL BiochemAnswering the narrow version, because the broad one does not have a single answer. The glucagon component looks paradoxical and is not. Glucagon receptor agonism raises energy expenditure and drives hepatic fatty-acid oxidation, and its hyperglycaemic tendency is offset by the GLP-1 arm's insulin secretagogue effect. Net result: intake down from GLP-1/GIP, expenditure up from glucagon, glycaemia neutral or improved. It is a balancing act, and it is why the liver-fat results are the most interesting part of the dataset.
Dr.RenalNash said:That holds where the measurement is reliable.
Second this. Nothing to add that would improve it.